Loop-Mediated Isothermal Amplification (LAMP) for Diagnosis of Endemic Febrile Illnesses in Resource-Limited Settings: A Narrative Review of Clinical Performance and Implementation Challenges

Abstract

Endemic Febrile Diseases (EFDs) such as dengue, malaria, and leptospirosis pose a significant diagnostic challenge in resource-limited settings (RLCs) due to overlapping clinical symptoms, leading to misdiagnosis and inappropriate treatment. While quantitative PCR (qPCR) offers high sensitivity, its reliance on complex hardware and stable electricity makes it unsuitable for RLCs. This narrative review evaluates the clinical performance of Loop-Mediated Isothermal Amplification (LAMP) as a viable alternative and explores recent innovations addressing its implementation barriers.

LAMP utilizes a strand-displacing polymerase and 4–6 primers to achieve rapid, 10⁹-fold amplification at a constant temperature, eliminating the need for a thermal cycler. Clinically, LAMP demonstrates high diagnostic accuracy, notably for Dengue Virus (DENV) and Malaria, offering comparable sensitivity to PCR but with operational advantages suitable for elimination programs. However, its adoption has been hampered by the complexity of nucleic acid extraction, the requirement for a cold chain for reagent stability, and issues of non-specific amplification and contamination.

To overcome these hurdles, transformative innovations have been developed, including "Direct LAMP" for extraction-free testing, lyophilization for cold-chain independence, and the use of biochemical additives (e.g., PEG) and hardware solutions (e.g., chip-based platforms) to enhance specificity and prevent contamination. Field implementation, such as the EXPANDIA project, confirms LAMP’s operational superiority in RLCs, highlighting its resilience during power outages and its potential for decentralized diagnostics. In conclusion, LAMP is maturing into a robust, point-of-care platform crucial for strengthening infectious disease surveillance and achieving universal health coverage.